Predicting efficacy and safety of the combination of hypertensive drugs using genetic and population data (360G-Wellcome-317540_Z_24_Z)

With the rise in hypertension prevalence, combination therapies involving multiple drug classes have become increasingly common. Despite current guidelines advocating for such combinations to control blood pressure, their long-term impacts remain inadequately assessed. This project aims to fill this gap by employing advanced genetic and observational analysis methods to assess the safety and efficacy of antihypertensive combinations. Using factorial Mendelian randomization, the research will analyse individual-level data from the UK Biobank to evaluate the combination effects of various hypertensive drugs like angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers, and thiazide or thiazide-like diuretics. Additionally, the project will apply a target trial emulation framework with electronic health record data. The mechanisms and risk factors associated with the identified effects will then be explored. By integrating findings with existing evidence, I seek to inform future hypertension guidelines and identify potential repurposing opportunities and safety concerns related to combination antihypertensive therapies. Keywords: antihypertensive drugs, combination therapy, factorial Mendelian randomization, electronic health records, target trial emulation.